tbuckley/cabot-search huggingface dataset:
Long-term outcomes of adolescents and young adults with testicular germ cell tumors: A population-based retrospective matched cohort study.
Authors: Rand Ajaj, Cindy Lau, Sumit Gupta, Nancy N. Baxter, Furqan Shaikh, Paul C. Nathan
Journal: Journal of Clinical Oncology (2023)

12016 Background: Testicular germ cell tumor (TGCT) survival exceeds 90%, but survivors of adult TGCT are at risk of developing late effects. Little is known about the risk for late effects in survivors of TGCT in children, adolescents, or young adults (CAYA). Methods: We identified all CAYA aged 11-21 years at TGCT diagnosis in Ontario, Canada, between 1992-2021. Those with complete treatment records were matched 1:5 by birth date and postal code at diagnosis to individuals from the general population (controls). Controls’ index date was defined as the diagnosis date of their survivor match. Participants were linked to health administrative databases to identify second malignant neoplasms (SMN); cardiovascular disease (CVD: congestive heart failure [CHF], myocardial infarction, coronary artery disease, pericardial disease, valvular abnormalities, arrhythmia, stroke, hypertension); renal disease (dialysis, kidney transplant); and hearing loss (physician-diagnosed hearing loss, hearing aid use). Cumulative incidences were compared between survivors and controls, and between chemotherapy and surgery treated survivors using Gray’s test. Cox proportional hazard models compared the risk of late effects between survivors and controls. Results: 521 TGCT survivors (296 chemotherapy treated, 225 treated with surgery only) were matched to 2605 controls. Median age at diagnosis/index date was 19 years. Survivors’ median follow-up time was 14.8 years (interquartile range: 10.7-21.7). Compared to controls, survivors had higher 15-year incidence and hazard ratio (HR) of all SMN (5.0% vs 0.5%; HR 8.4, p &lt; .0001), non-testicular SMN (2.1% vs 0.5%; HR 3.8, p = 0.0003), dialysis (1.0% vs 0.04%; HR 12.4, p = 0.003), kidney transplant (0.4% vs 0.0%, p = 0.002), hearing loss (7.1% vs 3.1%; HR 1.8, p = 0.005), and hearing aid use (1.0% vs 0.2%; HR 4.1, p = 0.02). Survivors were at substantially increased risk of any CVD (8.2% vs 5.5%; HR 1.4, p &lt; 0.03), CHF (1.2% vs. 0.2%; HR 5.0, p = 0.006), arrhythmia (1.8% vs 0.5%; HR 3.4, p = 0.002), and stroke (0.8% vs 0.05%; HR 8.7, p = 0.0006) despite no anthracycline exposure. Compared to surgery only treated survivors, chemotherapy treated survivors had higher 15-year incidence of any CVD (13.1% vs 2.0%, p &lt; 0.0001), CHF (2.1% vs 0.0%, p = 0.03), arrhythmia (3.3% vs 0.0%, p = 0.02), stroke (1.4% vs 0.0%, p = 0.02), hypertension (7.4% vs 2.0%, p = 0.009), and hearing loss (10.2% vs 3.0%, p = 0.02). Conclusions: Survivors of TGCT during CAYA are at considerable risk for late effects affecting multiple organ systems. In addition to previously described morbidities like hearing loss, survivors (particularly those who received chemotherapy) are at higher risk of CVD. Despite excellent rates of cure, TGCT survivors diagnosed at a young age require life-long risk-directed follow-up to maximize their long-term health.
Preliminary outcomes of a financial navigation program among lower socioeconomic patients with cancer.
Authors: Chiu Yi Joey Tan, Jessica Jacoby, Greg D. Garber, Amy Leader, Rebecca Cammy, Andrea Incudine, Morgan O’Brien, Rosie Cunningham, Thomas Stivers, Meredith Doherty
Journal: Journal of Clinical Oncology (2023)

12071 Background: Cancer patients receiving treatment are at risk of experiencing financial hardship, especially among those from lower socioeconomic status (SES) households. Patients experiencing financial toxicity are more likely to report poorer physical-wellbeing, higher anxiety, housing or food insecurity, and treatment non-adherence. While financial navigation programs are present, there is a lack of standardized practice to mitigate financial hardship among cancer patients. The purpose of this study is to evaluate the preliminary efficacy of Family Reach’s oncology financial treatment program (FTP) on financial toxicity, quality of life, and anxiety in low SES patients. FTP consists of individualized resource navigation, financial education services, and a $1000 patient assistance grant that was used towards non-treatment related expenses. Methods: 152 cancer patients undergoing active treatment, with household incomes under the 400% poverty line were recruited from two NCI-designated cancer centers. 99 participants completed the baseline and 2-month follow-up survey, consisting of these measures: COST: A FACIT Measure of Financial Toxicity (COST), Hospital Anxiety and Depression Scale (HADS), 36-Item Short Form Health Survey (SF-36), poverty exposers and treatment adherence items (secondary outcomes). Results: Participants were 69% female; roughly half (51%) were African American/Black, 34% were white, 4% were mixed, 3% were Asian and 8% reported ‘other’ or preferred not to answer. COST score at baseline (M=10.5, SD=6.4) significantly increased after 2 months (M=12.9, SD=7.9), t(176.2)= -2.3, p&lt;.05. HADS-Anxiety score at baseline (M=11.1, SD=4.7) significantly decreased after 2 months (M=9.2, SD=4.4), t(186.0)= 2.88, p&lt;.01. SF-36 Physical functioning score at baseline (M=34.0, SD=27.2) significantly increased after 2 months (M=43.9, SD=31.0), t(170.3)= -2.26, p&lt;.05. See Table for secondary outcomes. Conclusions: Early evidence of FTP indicates promising results to increase financial and physical well-being, and in reducing anxiety among lower SES cancer patients. FTP showed improvements in COST scores and reduced non-medical cost concerns. However, COST scores reported in this study are still lower compared to other studies. A planned future study involving monthly guaranteed income payments will be carried out to examine if financial well-being and treatment adherence can be achieved. Supported by: One Family Foundation/Social Impact Fund Secondary outcomes. [Table: see text]
SI-B003 (PD-1/CTLA-4) in patients with advanced solid tumors: A phase I study.
Authors: Yakun Wang, Yongsheng Li, Jiyan Liu, Su-xia Luo, Qi Li, Wen Zou, Zhaoxiang Wang, Yujia Peng, Sa Xiao, Hongwei Wang, Hai Zhu, Martin Sebastian Olivo, Yi Zhu, Lin Shen
Journal: Journal of Clinical Oncology (2023)

e14668 Background: Although marketed antibodies against PD-1/L1 or CTLA-4 have been shown to be efficacious in a variety of tumors, the overall response rate (ORR) remains low. SI-B003 is a PD-1/CTLA-4 bispecific antibody. We hypothesized that co-targeting PD-1 and CTLA-4 simultaneously could achieve a better anti-tumor activity due to cooperative binding to exhausted T-cell subsets. Methods: Patients with recurrent or metastatic solid tumors who had failed standard therapy were eligible to participate. SI-B003 was administered intravenously every other week (Q2W) in a four-week cycle. The phase Ia dose escalation consisted of an accelerated titration phase (the first 2 dose levels) and a mTPI-2 with a total of five dose levels: 0.1, 0.3→1.0, 3, 5 and 10 mg/kg. The phase Ib consisted of a dose expansion and indication expansion cohorts with 5, 10 mg/kg Q2W and 7.5mg/kg Q3W. The primary objectives of phase Ia were to assess dose-limiting toxicity (DLT), maximum tolerated dose (MTD) or maximum administration dose (MAD), and treatment emergent adverse events (TEAEs). The primary objectives of phase Ib included safety, tolerability, and identification of the recommended phase 2 dose (RP2D). Results: As of December 31, 2022, 60 patients with solid tumors received SI-B003 at six different dose levels (14 in Ia, 46 in Ib). Median age was 55.5 years. The median PFS (95%CI) was 3.7 (1.6~5.7) months. Among 56 evaluable patients, the objective response rate (ORR) (n/N, 95%CI) was 16.1% (9/56, 7.6~28.3%) and disease control rate (DCR) was 50.0% (28/56). Confirmed ORR, DCR, median duration of response (DoR) and median progression free survival (PFS) were 9.5% (2/21, 1.2~30.4%), 42.9% (9/21), NR and 2.1 (95%CI, 1.4~NA) months in the 5mg/kg Q2W group and 8.3% (2/24, 1.0~27.0%), 62.5% (15/24), 7.1 (95%CI, 1.9~NA) and 5.7 (95%CI, 1.9~8.7) months in 10mg/kg Q2W group respectively. One patient received 7.5mg/kg Q3W had a confirmed response and was still under treatment. Among 21 evaluable patients who had received prior PD-1/L1 treatment, the ORR and DCR were 14.3% (3/21, 3.1~36.3%) and 52.4% (11/21). The mDoR (95%CI) and mPFS (95%CI) were 4.2 (NA) months and 4.1 (1.4, 5.7) months. The most common TRAEs were rash (35%), AST increased (28%), ALT increased (28%). The most common grade ≥3 TRAEs were AST increased (3%). One patient died from an immune-mediated pneumonia. Conclusions: SI-B003 demonstrated a tolerable safety profile and preliminary anti-tumor activity in patients with recurrent or metastatic solid tumors. Anti-tumor effects of SI-B003 were observed in patients who had progressed on prior PD-1/L1 immunotherapy suggesting that SI-B003 may be beneficial for patients who have developed resistance to PD-1/L1 drugs. Clinical trial information: NCT04606472 .
Subgroup analysis of double-blind, placebo-controlled Ph. 2 study of nanvuranlat in treatment of pre-treated, advanced, refractory biliary tract cancer (BTC): Patients with high LAT1 expression and response to nanvuranlat.
Authors: Masafumi Ikeda, Makoto Ueno, Masayuki Furukawa, Chigusa Morizane, Tetsuo Takehara, Tomohiro Nishina, Akiko Todaka, Naohiro Okano, Kazuo Hara, Yousuke Nakai, Kazuyoshi Ohkawa, Takashi Sasaki, Kazuya Sugimori, Naoyuki Yokoyama, Kouji Yamamoto, Junji Furuse
Journal: Journal of Clinical Oncology (2023)

4011 Background: L-type amino acid transporter 1 (LAT1, SLC7A5) is overexpressed in cancer cells leading to aggressive proliferation and lymphatic metastases. LAT1 sustains energy resources by supplying essential amino acids to the TCA cycle in chemotherapy-resistant cancer cells. LAT1 is a documented marker of poor prognosis. In a placebo-controlled, randomized trial involving patients with pre-treated, advanced, refractory biliary tract cancer (BTC), monotherapy with nanvuranlat (JPH203), a selective LAT1 inhibitor, demonstrated a significant improvement in progression free survival (PFS) compared to placebo. Subgroup analysis was conducted to determine whether the level of expression of LAT1 affects nanvuranlat efficacy. Methods: Patients with four different subtypes of advanced BTC were enrolled: intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder and ampulla of Vater cancers. All were refractory to or intolerant of standard chemotherapy and other investigational medicines. Our analysis compared efficacy and safety in the subgroup with high LAT1 expression and all patients group. LAT1 expression was immunohistochemically evaluated in tumor specimens of BTC patients at baseline, as defined by Yanagisawa N, et al. (Cancer Med 2014). Results: At data cut-off (Feb 28, 2022), 211 BTC patients consented at 14 centers in Japan, and 104 patients were randomized (2:1) to nanvuranlat (n = 69) or placebo (n = 35) as the full analysis set (FAS) population. Among the samples immunohistochemically evaluable for LAT1, 62.5% had high LAT1 expression. There was no significant difference in background demography between all patient group and the high-LAT1 subgroup. Nanvuranlat met its primary endpoint (FAS by the blinded independent central review (BICR)), demonstrating a statistically significant improvement in PFS by BICR in comparison with the placebo group. The hazard ratios were further improved with nanvuranlat versus placebo, on analysis of the high-LAT1 subgroup of patients in both PFS and OS. Safety was comparable between nanvuranlat and placebo, on analysis of the high-LAT1 subgroup. Conclusions: This subgroup analysis indicates that the efficacy of nanvuranlat in PFS and OS is enhanced in BTC patients with high LAT1 expression, when compared with placebo. Safety profiles were similar for nanvuranlat- and placebo-treated patients in this subgroup analysis. Clinical trial information: UMIN000034080 . [Table: see text]
miRNAs targeting RAS and their clinical relevance in resected pancreatic adenocarcinoma (PC): Results from a prospective study.
Authors: Daniele Lavacchi, Enrico Caliman, Serena Pillozzi, Simone Polvani, Federico Scolari, Anna Boddi, Adriano Pasqui, Sara Fancelli, Elisa Giommoni, Elisa Pellegrini, Agnese Vannini, Marco Brugia, Lavinia Pugliese, Luca Messerini, Antonio Taddei, Luca Moraldi, Andrea Galli, Lorenzo Antonuzzo
Journal: Journal of Clinical Oncology (2023)

e16314 Background: Pancreatic adenocarcinoma (PC) is one of the big killers with a 5-year disease-free survival (DFS) rate of 19-26% after resection despite adjuvant treatments. KRAS mutations have been reported in approximately 90% of PC cases and, beyond KRAS activation by gene mutations, several miRNAs directly targeting KRAS have been reported to be simultaneously downregulated, strengthening the already activated RAS signaling. In addition, the interplay between miRNAs and RAS includes downstream miRNA effectors whose role needs to be elucidated. The aim of this study was to evaluate the expression of candidate miRNAs strictly related to KRAS expression in order to elucidate the prognostic value. Methods: In this single-center observational prospective study we included patients with pathologically confirmed PC, who underwent radical surgery and were referred to the Clinical Oncology Unit, Careggi University Hospital, Florence (Italy), between 2015 and 2022. Total RNA was extracted from FFPE sections, retro-transcribed and the resulting cDNA was then used for qPCR analysis. Results: Among 44 patients included in the study, 34.1% were male and 65.9% female (median age 75 years). The majority of cases had the primary tumor located at the head of the pancreas (65.9%) and the pathological stage was pT1-2 in 45.5%, pT3 in 54.5%, pN0 in 22.7%, pN+ in 77.3%. Overall, 63.6% of patients received adjuvant chemotherapy and 69.0% experienced disease recurrence. Twenty-three specimens were adequate for miRNA analysis. A different expression of the three target miRNAs between PC and healthy tissue was observed: miR-155 was overexpressed and miR-206 downregulated in PC, while miR-143 had a similar expression in both tissues. miR-143 overexpression was associated with nodal involvement (pN+) at the pathological examination (p = 0.029). Among clinicopathological features, pN+ was associated with shorter DFS (p = 0.009) and overall survival (OS) (p = 0.021) compared to pN0. A trend toward inferior DFS was observed for higher expression of miR-206 (p = 0.095) and miR-143 (p = 0.092). Among patients receiving a first-line treatment for advanced disease, miR-155 was overexpressed in responders vs non-responders (p = 0.048). Conclusions: miRNA expression is involved in tumorigenesis and metastatic spread in PC. A comprehensive analysis of the miRNA-RAS interplay deserves to be further investigated as a predictor of clinical outcome, especially for miR-143 overexpression which was associated with lymphatic spread and, consequently, poor prognosis.
High rates of detection of metastatic/recurrent colorectal cancer on clinical imaging at the time of molecular residual disease testing following operative management.
Authors: Danny Trotier, Kayla Lemmon, Danielle Golner, Maddie Buratti, Alyssa DeZeeuw, Noelle K. LoConte, Sam Joseph Lubner, Nataliya Volodymyrivna Uboha, Jeremy D. Kratz, Monica Arun Patel, Evie Carchman, Kristina A. Matkowskyj, Wei Zhang, Mark E. Burkard, Dustin A. Deming
Journal: Journal of Clinical Oncology (2023)

e15543 Background: Detection of circulating tumor DNA (ctDNA) following operative management for colorectal cancer (CRC) as part of molecular residual disease (MRD) assays has shown significant prognostic implications. The majority of studies examining the time to detection of cancer recurrence have been done retrospectively without the treating physician knowing the results of the assay. Limited prospective data exists regarding the probability of detecting cancer on imaging at the time of a positive MRD test following operative management of all sites of disease. Here, we analyze the association of positive MRD testing with imaging findings of recurrent or metastatic CRC using a cohort of patients that underwent prospective MRD testing. Methods: Patients with stage I-IV intestinal cancers at University of Wisconsin Carbone Cancer Center who underwent prospective Natera Signatera MRD testing following operative management of their disease were identified and consented to an IRB-approved registry protocol. Those consented patients who had a positive test without being on systemic therapy and had clinical imaging within 45 days were analyzed further. The presence of definitive cancer, indeterminate findings, and no evidence of cancer was recorded per the treating physician using standard of care clinical imaging. The presence of cancer on imaging was then correlated with the quantity of ctDNA (mean tumor molecules (MTM)/ml). Results: 163 patients with stage I-IV CRC and 1 small intestinal cancer underwent MRD testing. 30 positive ctDNA tests with imaging were available across 22 unique patients (median age 54 years (29-84) 7 females). 23 samples were in the resected metastatic setting, 5 stage III and 2 stage I. Cancer was seen on imaging in 19/30 (63%) of positive tests, indeterminate in 3 (10%) and negative for cancer in 9/30 (27%). With ctDNA levels &gt; 10 MTM/ml (n = 7), cancer was detected on imaging in all cases. With ctDNA levels of 1-10 MTM/ml cancer was detected in 42% and at &lt; 1 MTM/ml in 64%. A trend towards greater detection of cancer was observed when MRI or PET/CT was performed. Radiologic disease detection in patients with positive MRD analysis was higher in those with stage IV disease (70%) vs. stage I-III (43%). Conclusions: ctDNA MRD positivity is associated with high rates of detection of recurrent/metastatic CRC, especially in patients with resected stage IV disease and with a quantity of &gt; 10 MTM/ml. Clinical imaging should be considered at the time of detection of ctDNA.
Meta-analysis of gastrointestinal adverse effects in patients with non-small cell lung cancer treated with a combination therapy of pembrolizumab and chemotherapy versus chemotherapy alone.
Authors: Akshita Khosla, Samiran Mukherjee, Jean Marie Koka, Stephen Arthur Shore
Journal: Journal of Clinical Oncology (2023)

e14634 Background: Pembrolizumab combined with chemotherapy has transformed the treatment of non-small cell lung cancer (NSCLC) and is now the standard of care. It has unique immune-related adverse events (irAE) that have been well defined. There is limited literature reporting its effect on the occurrence of common chemotherapy related AEs such as gastrointestinal adverse effects (GIAEs) (nausea, vomiting and diarrhea). We performed a meta-analysis to evaluate the GIAEs of pembrolizumab in non-small cell lung cancer patients treated with pembrolizumab and chemotherapy (P+C) and drew a comparison with those treated with chemotherapy alone (C). Methods: A literature search was performed in the MEDLINE database for randomized clinical trials of non-small cell lung cancer treated with pembrolizumab reporting gastrointestinal adverse effects. Articles were screened in concordance with PRISMA guidelines. Funnel plots were generated to assess publication bias. The pooled odds ratios (OR) for occurrence of GIAEs with 95% confidence intervals (CI) using random-effects models was calculated. Results: 9 studies (including data from KEYNOTE-021, 407, 189, 604, PROLUNG trial) were included in our analyses (n = 3157 patients). A clear increment in certain GIAEs (constipation (OR 1.16 (0.99- 1.37)), diarrhea (OR 1.51 (1.28- 1.78)), colitis (OR 4.39 (1.81- 10.62)), hepatitis (OR 4.67(1.79-12.18)) was noted the Pembrolizumab plus chemotherapy arm versus chemotherapy alone. No significant differences were noted in the occurrence of nausea, vomiting and pancreatitis. Conclusions: Pembrolizumab plus chemotherapy compared with chemotherapy alone has been studied extensively to highlight the survival advantages of the former therapeutic strategy. The risk of certain GIAEs (constipation, diarrhea, colitis, hepatitis) with pembrolizumab combination therapy for non-small cell lung cancer is significantly higher in comparison to chemotherapy alone. This alludes to the superadded effect of pembrolizumab on the existing AEs of chemotherapy. [Table: see text]
Retrospective study of combined pelvic organ resection in the treatment of primary and recurrent pelvic malignant tumors.
Authors: Li Zhenyu, Yuzhou Zhao, Changzheng Li
Journal: Journal of Clinical Oncology (2023)

e15635 Background: For locally advanced or recurrent pelvic malignancies, combined pelvic organ resection has been used to treat rectal, bladder, gynecological and other related malignancies. As an interdisciplinary and high-risk operation, the perioperative safety and future information are often very limited. We retrospectively analyzed the efficacy of PE surgery in our institution. Methods: In this retrospective study, 59 patients with pelvic malignant tumors received PE surgery from July 2015 to July 2021. They were divided into two groups according to the location of the disease: rectal tumor group (n = 40) and cervical cancer group (n = 19). The baseline data, gene detection reports, pathological reports, perioperative conditions and prognosis were analyzed. The two groups were compared by independent sample t-test; Comparison between groups χ2 test, the survival curve was drawn by Kaplan-Meier method and compared by log rank test. Results: Among these 59 patients treated with PE, the rectal tumor group and the cervical cancer group did not differ significantly in terms of demographics, operative time, hospital stay, intraoperative blood loss, and rates of use of preoperative and intraoperative radiotherapy. Compared with the two groups, the overall incidence of postoperative complications was 37% in the group with rectal tumours and 26% in the group with perineal wound infection being the most common, cervical cancer 46% and urinary tract infection being the most common. Comparing the postoperative survival OS between patients in the rectal tumor group and those in the cervical cancer group, the former was better, with 5-year overall survival rates of 37% in the rectal tumor group and 28% in the cervical cancer group. Within the group of rectal tumours, however, there are differences in survival between patients with primary (LARC) and recurrent (lrrc) rectal tumours; Patients with LARC have shown a significant survival benefit postoperatively, with 5-year overall survival rates of 40% for patients with LARC and 27% for patients with lrrc. OS was significantly better in patients with well differentiated tumors, N0 stage, and high microsatellite instability (MSI). On the basis of univariate analysis, poorly differentiated tumor, regional lymph node dissemination, MSI, and no chemotherapy received perioperatively were significant predictors of poor survival (P &lt; 0.05). Conclusions: PE is currently an effective treatment for pelvic malignancies with aggressive radical resection of lesions, which can effectively improve their cure rate, improve quality of life, and careful patient selection can optimize outcomes.